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The purpose of this study is to find out if tadalafil can help overweight and obese people metabolize blood sugar more efficiently. The investigators also want to find out if 20 mg/day of tadalafil for 3 months is safe to take without causing too many side effects. The investigators are plan to enroll 100 subjects at Massachusetts General Hospital (MGH).
This study is examining changes in insulin resistance and glucose tolerance following 3 months of treatment with oral, once daily tadalafil.
The investigators primary hypotheses are that measurable decreases in insulin resistance (as measured by HOMA-IR) and increases in insulin sensitivity (as measured by the Matsuda index) will occur following 3 months of treatment with oral tadalafil 20 mg daily compared to placebo.
The investigators secondary hypotheses are that improvements in average glycemia (as measured by hemoglobin A1C), pancreatic beta cell function (as measured by the oral disposition index), and body composition (including weight, waist circumference, body mass index, and waist-hip ratio) will occur as a result of tadalafil-mediated changes in the cGMP pathway.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tadalafil | Active Comparator | 20 mg Tadalafil tablet taken by mouth once a day for 3 months |
|
| Placebo | Placebo Comparator | Placebo tablet taken by mouth once a day for 3 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tadalafil | Drug | 20 mg Tadalafil taken once a day for 3 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Insulin Resistance From Baseline to 3 Months, as Measured by HOMA-IR | The primary endpoint is defined as the treatment group difference in the change in insulin resistance (baseline HOMA-IR minus 3-month HOMA-IR). HOMA-IR = [fasting glucose * fasting insulin]/405 | Baseline and 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline to 3-month Change in Insulin Sensitivity, as Measured by the Matsuda Index | The secondary endpoint is defined as the treatment group difference in the change in Matsuda Index (baseline minus 3-month). This index is a measure of insulin resistance derived from a frequently sampled oral glucose tolerance test, obtaining glucose and insulin levels in the fasting state, as well as 30, 60, 90, and 120 min after administration of oral glucose load. Matsuda index = 10,000/SQRT [fasting glucose*fasting insulin* (mean glucose from time 30, 60, 90, 120 min) * (mean insulin at time 30, 60, 90, and 120 min)] |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas J Wang, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25213566 | Derived | Ho JE, Arora P, Walford GA, Ghorbani A, Guanaga DP, Dhakal BP, Nathan DI, Buys ES, Florez JC, Newton-Cheh C, Lewis GD, Wang TJ. Effect of phosphodiesterase inhibition on insulin resistance in obese individuals. J Am Heart Assoc. 2014 Sep 11;3(5):e001001. doi: 10.1161/JAHA.114.001001. |
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111 participants screened, 38 excluded (34 did not meet eligibility criteria, 2 unable to obtain intravenous access, 2 withdrew consent)
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| ID | Title | Description |
|---|---|---|
| FG000 | Tadalafil | 20 mg Tadalafil tablet taken by mouth once a day for 3 months Tadalafil: 20 mg Tadalafil taken once a day for 3 months |
| FG001 | Placebo | Placebo tablet taken by mouth once a day for 3 months Placebo: Placebo tablet taken by mouth once a day for 3 months |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Tadalafil | 20 mg Tadalafil tablet taken by mouth once a day for 3 months Tadalafil: 20 mg Tadalafil taken once a day for 3 months |
| BG001 | Placebo | Placebo tablet taken by mouth once a day for 3 months Placebo: Placebo tablet taken by mouth once a day for 3 months |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Insulin Resistance From Baseline to 3 Months, as Measured by HOMA-IR | The primary endpoint is defined as the treatment group difference in the change in insulin resistance (baseline HOMA-IR minus 3-month HOMA-IR). HOMA-IR = [fasting glucose * fasting insulin]/405 | Posted | Mean | Standard Deviation | mg*microunits/dL*mL | Baseline and 3 months |
|
Adverse events recorded during study duration (3 months)
Adverse events ascertained at each follow-up visit
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tadalafil | 20 mg Tadalafil tablet taken by mouth once a day for 3 months Tadalafil: 20 mg Tadalafil taken once a day for 3 months |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Vascular disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jennifer Ho | Massachusetts General Hospital | 617-726-6411 | jho1@partners.org |
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| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D007333 | Insulin Resistance |
| D018149 | Glucose Intolerance |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000068581 | Tadalafil |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D002243 | Carbolines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo | Drug | Placebo tablet taken by mouth once a day for 3 months |
|
|
| Baseline and 3 months |
| Baseline to 3-month Change in Endothelial Function Measured by EndoPAT | Endothelial function was measured using the reactive hyperemia index, acquired using EndoPAT device. Peripheral arterial tonometry probes were placed on both index fingers. After a 5 min equilibration period, a blood pressure cuff was inflated to 200 mmHg and kept inflated for 5 min. The cuff was then rapidly deflated and the reactive hyperemic response pulse volume recorded, where RHI = ratio of hyperemic finger pulse volume (post-cuff inflation / pre-cuff inflation) to control finger pulse volume (post-cuff inflation / pre-cuff inflation) | Baseline and 3 months |
| Insulinogenic Index | The secondary endpoint is defined as the treatment group difference in the change in insulinogenic index (baseline minus 3-month). This index is thought to reflect insulin secretion, and is derived from fasting and 30 min-post oral glucose tolerance testing glucose and insulin values. Insulinogenic index = [fasting insulin - insulin at time 30 min] / [fasting glucose - glucose at time 30 min] | Baseline and 3 months |
| Baseline to 3 Month Change in Composite of Insulin Resistance and Sensitivity, as Measured by the Oral Disposition Index | The secondary endpoint is defined as the treatment group difference in the change in oral disposition index (baseline minus 3-month). This is thought to reflect a composite of both insulin resistance and secretion. Oral disposition index = insulinogenic index / fasting insulin | Baseline and 3 months |
| Baseline to 3-month Change in Matsuda Disposition Index | Change in disposition index from baseline to 3 months. This index is a composite measure thought to reflect insulin resistance and secretion. Matsuda disposition index = [Matsuda sensitivity index * insulinogenic index] | Baseline and 3 months |
| Non-fasting |
|
| Missing data |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Gender | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body mass index | Mean | Standard Deviation | kg/m^2 |
|
| Fasting insulin | Mean | Standard Deviation | microunits/mL |
|
|
|
|
| Secondary | Baseline to 3-month Change in Insulin Sensitivity, as Measured by the Matsuda Index | The secondary endpoint is defined as the treatment group difference in the change in Matsuda Index (baseline minus 3-month). This index is a measure of insulin resistance derived from a frequently sampled oral glucose tolerance test, obtaining glucose and insulin levels in the fasting state, as well as 30, 60, 90, and 120 min after administration of oral glucose load. Matsuda index = 10,000/SQRT [fasting glucose*fasting insulin* (mean glucose from time 30, 60, 90, 120 min) * (mean insulin at time 30, 60, 90, and 120 min)] | Posted | Mean | Standard Deviation | unitless index | Baseline and 3 months |
|
|
|
|
| Secondary | Baseline to 3-month Change in Endothelial Function Measured by EndoPAT | Endothelial function was measured using the reactive hyperemia index, acquired using EndoPAT device. Peripheral arterial tonometry probes were placed on both index fingers. After a 5 min equilibration period, a blood pressure cuff was inflated to 200 mmHg and kept inflated for 5 min. The cuff was then rapidly deflated and the reactive hyperemic response pulse volume recorded, where RHI = ratio of hyperemic finger pulse volume (post-cuff inflation / pre-cuff inflation) to control finger pulse volume (post-cuff inflation / pre-cuff inflation) | Posted | Mean | Standard Deviation | unitless index | Baseline and 3 months |
|
|
|
|
| Secondary | Insulinogenic Index | The secondary endpoint is defined as the treatment group difference in the change in insulinogenic index (baseline minus 3-month). This index is thought to reflect insulin secretion, and is derived from fasting and 30 min-post oral glucose tolerance testing glucose and insulin values. Insulinogenic index = [fasting insulin - insulin at time 30 min] / [fasting glucose - glucose at time 30 min] | Posted | Mean | Standard Deviation | unitless index | Baseline and 3 months |
|
|
|
|
| Secondary | Baseline to 3 Month Change in Composite of Insulin Resistance and Sensitivity, as Measured by the Oral Disposition Index | The secondary endpoint is defined as the treatment group difference in the change in oral disposition index (baseline minus 3-month). This is thought to reflect a composite of both insulin resistance and secretion. Oral disposition index = insulinogenic index / fasting insulin | Posted | Mean | Standard Deviation | unitless index | Baseline and 3 months |
|
|
|
|
| Secondary | Baseline to 3-month Change in Matsuda Disposition Index | Change in disposition index from baseline to 3 months. This index is a composite measure thought to reflect insulin resistance and secretion. Matsuda disposition index = [Matsuda sensitivity index * insulinogenic index] | Posted | Mean | Standard Deviation | unitless index | Baseline and 3 months |
|
|
|
|
| 0 |
| 36 |
| 7 |
| 36 |
| EG001 | Placebo | Placebo tablet taken by mouth once a day for 3 months Placebo: Placebo tablet taken by mouth once a day for 3 months | 0 | 37 | 2 | 37 |
| Blurry vision and headache | Vascular disorders | Systematic Assessment |
|
| Back or leg pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Headache and back ache | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| arm pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
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| D006943 | Hyperglycemia |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D026121 |
| Indole Alkaloids |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D002241 | Carbohydrates |